DNA methylation is critical for tooth agenesis: implications for sporadic non-syndromic anodontia and hypodontia

Abstract

Hypodontia is caused by interactions among genetic, epigenetic, and environmental factors during tooth development, but the actual mechanism is unknown. DNA methylation now appears to play a significant role in abnormal developments, flawed phenotypes, and acquired diseases. Methylated DNA immunoprecipitation (MeDIP) has been developed as a new method of scanning large-scale DNA-methylation profiles within particular regions or in the entire genome. Here, we performed a genome-wide scan of paired DNA samples obtained from 4 patients lacking two mandibular incisors and 4 healthy controls with normal dentition. We scanned another female with non-syndromic anodontia and her younger brother with the same gene mutations of the PAX9,MSX1,AXIN2 and EDA, but without developmental abnormalities in the dentition. Results showed significant differences in the methylation level of the whole genome between the hypodontia and the normal groups. Nine genes were spotted, some of which have not been associated with dental development; these genes were related mainly to the development of cartilage, bone, teeth, and neural transduction, which implied a potential gene cascade network in hypodontia at the methylation level. This pilot study reveals the critical role of DNA methylation in hypodontia and might provide insights into developmental biology and the pathobiology of acquired diseases.

SP1 regulates KLF4 via SP1 binding motif governed by DNA methylation during odontoblastic differentiation of human dental pulp cells

“…Mir‐143 and mir‐145 have been proven to regulate odontoblastic differentiation in a posttranscriptional manner . DNA methylation and histone modification have also been reported to have some effects in tooth‐related cells . Recent study indicated a potential role of DNA methylation in odontoblastic differentiation of hDPCs as knockdown of TET1 would suppress odontoblastic differentiation through attenuated hydroxymethylation and transcription of FAM20C.…”

Genetic study of non‐syndromic tooth agenesis through the screening of paired box 9, msh homeobox 1, axin 2, and Wnt family member 10A genes: a case‐series

“…Our study results confirm previous findings indicating that tooth agenesis depends on variability of the ethnic population. We also stipulated that NSTA phenotypic variability in the case of the same disease‐causing mutation could be explained by the presence of polymorphisms or epigenetic alterations . Therefore, we hypothesize that a specific tooth‐agenesis phenotype could be the result of a specific combination of mutation(s) and/or polymorphism(s) in one or several genes involved in the early stages of tooth development.…”

PAX9 gene mutations and tooth agenesis: A review

“…The 9 genes with highest differences in methylation status have undergone further research including NFκBIB, PRKCD, Hey1 CACNA1A. All these genes are related to cell signalling pathways important during tissue and organ development …”